title: Effects of pirfenidone on increased cough reflex sensitivity in guinea pigs.
abstract: Pirfenidone, an antifibrotic drug with anti-inflammatory and antioxidant effects, delays fibrosis in idiopathic pulmonary fibrosis (IPF). Patients with IPF have a greater cough reflex sensitivity to inhaled capsaicin than healthy people, and cough is an independent predictor of IPF disease progression; however, the effects of pirfenidone on cough reflex sensitivity are unknown. After challenge with an aerosolized antigen in actively sensitized guinea pigs, pirfenidone was administered intraperitoneally, and the cough reflex sensitivity was measured at 48 h after the challenge. Bronchoalveolar lavage (BAL) was performed, and the tracheal tissue was collected. Pirfenidone suppressed the capsaicin-induced increase in cough reflex sensitivity in a dose-dependent manner. Additionally, increased levels of prostaglandin E2, substance P, and leukotriene B4, but not histamine, in the BAL fluid were dose dependently suppressed by pirfenidone. The decrease in neutral endopeptidase activity in the tracheal tissue was also alleviated by pirfenidone treatment. The total number of cells and components in the BAL fluid was not influenced. These results suggest that pirfenidone ameliorates isolated cough based on increased cough reflex sensitivity associated with allergic airway diseases, and potentially relieve chronic cough in IPF patients who often have increased cough reflex sensitivity. Prospective studies on cough-relieving effects of pirfenidone in patients with IPF are therefore warranted.
authors.affiliation: Department of Respiratory Medicine, Cellular Transplantation Biology, Graduate School of Medicine, Kanazawa University, 13-1, Takara-machi, Kanazawa 920-8641, Japan. akihito@staff.kanazawa-u.ac.jp
authors.forename: Akihito
authors.initials: A
authors.lastname: Okazaki
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ohkura
authors.forename: Masaki
authors.initials: M
authors.lastname: Fujimura
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Katayama
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kasahara
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D000941:Antigens / Q000276:immunology; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D002211:Capsaicin / Q000276:immunology; D003371:Cough / Q000276:immunology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D015260:Neprilysin / Q000378:metabolism; D011728:Pyridones / Q000008:administration & dosage / Q000494:pharmacology*; D012018:Reflex / Q000187:drug effects; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000941:Antigens; D011728:Pyridones; C093844:pirfenidone; D015260:Neprilysin; D002211:Capsaicin
keywords: Cough reflex sensitivity; Idiopathic pulmonary fibrosis; Neutral endopeptidase; Pirfenidone; Prostaglandin E(2); Substance P